Abstract
Background Antipsychotics are commonly used in the elderly despite a lack of safety data from randomized trials, particularly for the typical antipsychotics. Observational studies have investigated the association between antipsychotics and stroke but results vary, which may be due to lack of control for unmeasured confounding.
Objective To estimate the risk of hospitalization for stroke in elderly users of antipsychotics.
Study Design and Setting Using the Australian Government Department of Veterans’ Affairs administrative claims dataset we utilized a self-controlled case series design to risk-adjust for potential unmeasured confounding. Risk periods prior to antipsychotic initiation were also included to search for evidence of confounding by indication. Unexposed patients were included to adjust for the increasing incidence of hospitalization for stroke with age.
Results There were 10 638 patients aged ≥65 years with at least one hospitalization for stroke identified during the 4-year period from 1 January 2003 to 31 December 2006. Of these, 514 patients were initiated on typical antipsychotics and 564 patients were initiated on atypical antipsychotics. Hospitalization for stroke was increased in the first week after initiation of a typical antipsychotic (incidence rate ratio [IRR] 2.3; 95% CI 1.3, 3.8). There was no evidence of an increased risk of hospitalization for stroke after initiation of atypical antipsychotics. The risk of hospitalization for stroke progressively increased in the weeks leading up to first-time antipsychotic treatment. However, while the risk of hospitalization for stroke in the week prior to initiating antipsychotic therapy was significantly increased for patients initiated on typical antipsychotics (IRR 7.2; 95% CI 5.3, 9.8), patients initiated on atypical antipsychotics had no excess risk in the same period (IRR 1.2; 95% CI 0.7, 2.3).
Conclusions The results of this study are consistent with randomized controlled trial evidence indicating that there is no increased risk of serious cerebrovascular events requiring hospitalization in patients taking atypical antipsychotics. No randomized controlled trial evidence is available on the risk of hospitalization for stroke with use of typical antipsychotics in the elderly. This study found a small but significantly increased risk of hospitalization for stroke immediately following the initiation of typical antipsychotics. Antipsychotics are likely to be initiated after hospitalization for stroke. This practice is likely to reflect the prescribing of antipsychotics during hospital admission for post-stroke complications such as delirium; however, the long-term effects of this practice are unknown.
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References
Australian Government, Department of Health and Ageing. Australian statistics on medicines [online]. Available from URL: http://www.health.gov.au/internet/main/publishing.nsf/Content/pbs-pubs-asm2007 [Accessed 2010 Sep 2]
Ballard C, Fossey J, Sharp S. Antipsychotics in patients with Alzheimer’s disease: what is their clinical value? Nat Clin Pract Neurol 2007; 3: 248–9
De Deyn PP, Katz IR, Brodaty H, et al. Management of agitation, aggression, and psychosis associated with dementia: a pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone. Clin Neurol Neurosurg 2005; 107: 497–508
Katz I, de Deyn PP, Mintzer J, et al. The efficacy and safety of risperidone in the treatment of psychosis of Alzheimer’s disease and mixed dementia: a meta-analysis of 4 placebo-controlled clinical trials. Int J Geriatr Psychiatry 2007; 22: 475–84
Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006; 14: 191–210
Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006; 355: 1525–38
How safe are antipsychotics in dementia? Drug Ther Bull 2007; 45: 81–5
Australian Government, Department of Health and Ageing. Schedule of pharmaceutical benefits: PBS for health professionals [online]. Available from URL: http://www.pbs.gov.au/html/healthpro/home [Accessed 2010 Sep]
Ballard C, Waite J. The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer’s disease. Cochrane Database Syst Rev 2006; (1): CD003476
Herrmann N, Lanctot KL. Do atypical antipsychotics cause stroke? CNS Drugs 2005; 19: 91–103
Kolanowski A, Fick D, Waller JL, et al. Outcomes of anti-psychotic drug use in community-dwelling elders with dementia. Arch Psychiatr Nurs 2006; 20: 217–25
Barnett MJ, Wehring H, Perry PJ. Comparison of risk of cerebrovascular events in an elderly VA population with dementia between antipsychotic and nonantipsychotic users. J Clin Psychopharmacol 2007; 27: 595–601
Sacchetti E, Trifiro G, Caputi A, et al. Risk of stroke with typical and atypical anti-psychotics: a retrospective cohort study including unexposed subjects. J Psychopharmacol 2008; 22: 39–46
Douglas IJ, Smeeth L. Exposure to antipsychotics and risk of stroke: self controlled case series study. BMJ 2008; 337: a1227
Sacchetti E, Turrina C, Cesana B, et al. Timing of stroke in elderly people exposed to typical and atypical antipsychotics: a replication cohort study after the paper of Kleijer et al. J Psychopharmacol 2009 Jul; 24(7): 1131–2
Kleijer BC, van Marum RJ, Egberts AC, et al. Risk of cerebrovascular events in elderly users of antipsychotics. J Psychopharmacol 2009 Nov; 23(8): 909–14
Herrmann N, Mamdani M, Lanctot KL. Atypical antipsychotics and risk of cerebrovascular accidents. Am J Psychiatry 2004; 161: 1113–5
Gill SS, Rochon PA, Herrmann N, et al. Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ 2005; 330: 445
Finkel S, Kozma C, Long S, et al. Risperidone treatment in elderly patients with dementia: relative risk of cerebrovascular events versus other antipsychotics. Int Psychogeriatr 2005; 17: 617–29
Wang PS, Schneeweiss S, Setoguchi S, et al. Ventricular arrhythmias and cerebrovascular events in the elderly using conventional and atypical antipsychotic medications. J Clin Psychopharmacol 2007; 27: 707–10
Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs atypical antipsychotic medications. N Engl J Med 2005; 353: 2335–41
Hallas J. Pharmacoepidemiology: current opportunities and challenges. Norweg J Epidemiol 2001; 11: 7–12
Schneeweiss S, Setoguchi S, Brookhart A, et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007; 176: 627–32
Hollis J, Grayson D, Forrester L, et al. Antipsychotic medication dispensing and risk of death in veterans and war widows 65 years and older. Am J Geriatr Psychiatry 2007; 15: 932–41
Whitaker HJ, Farrington CP, Spiessens B, et al. Tutorial in biostatistics: the self-controlled case series method. Stat Med 2006; 25: 1768–97
World Health Organization Collaborating Centre for Drug Statistics Methodology. Anatomical therapeutic chemical code classification index with defined daily doses [online]. Available from URL: http://www.whocc.no/atcddd/ [Accessed 2010 Sep 2010]
The international statistical classification of diseases and related health problems, 10th revision, Australian modification (ICD-10-AM). 6th ed. Sydney (NSW): National Centre for Classification in Health, 2005
Whitaker HJ, Hocine MN, Farrington CP. The methodology of self-controlled case series studies. Stat Methods Med Res 2009 Feb; 18(1): 7–26
Hubbard R, Lewis S, West J, et al. Bupropion and the risk of sudden death: a self-controlled case-series analysis using the Health Improvement Network. Thorax 2005; 60: 848–50
McManus J, Pathansali R, Stewart R, et al. Delirium post-stroke. Age Ageing 2007; 36: 613–8
Oldenbeuving AW, de Kort PL, Jansen BP, et al. Delirium in acute stroke: a review. Int J Stroke 2007; 2: 270–5
eTG complete. Melbourne (VIC): Therapeutic Guidelines Ltd, 2010
Normand SL, Sykora K, Li P, et al. Readers guide to critical appraisal of cohort studies: 3. Analytical strategies to reduce confounding. BMJ 2005; 330: 1021–3
Liperoti R, Onder G, Lapane KL, et al. Conventional or atypical antipsychotics and the risk of femur fracture among elderly patients: results of a case-control study. J Clin Psychiatry 2007; 68: 929–34
Hugenholtz GW, Heerdink ER, van Staa TP, et al. Risk of hip/femur fractures in patients using antipsychotics. Bone 2005; 37: 864–70
Pouwels S, van Staa TP, Egberts AC, et al. Antipsychotic use and the risk of hip/femur fracture: a population-based case-control study. Osteoporos Int 2009 Sep; 20(9): 1499–506
Farrington CP, Whitaker HJ. Semiparametric analysis of case series data. Appl Stat 2006; 55: 553–94
Acknowledgements
This research was funded by the Australian Government Department of Veterans’ Affairs as part of the Veterans’ Medicines Advice and Therapeutics Education Services (Veterans’ MATES) project. The authors have no conflicts of interest that are directly relevant to the content of this study.
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Pratt, N.L., Roughead, E.E., Ramsay, E. et al. Risk of Hospitalization for Stroke Associated with Antipsychotic Use in the Elderly. Drugs Aging 27, 885–893 (2010). https://doi.org/10.2165/11584490-000000000-00000
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DOI: https://doi.org/10.2165/11584490-000000000-00000